The work proposed here will continue to explore and demonstrate the range of applications of the effects of non-diamagnetic agents on the two strongest tissue NMR signals: those of 1H2O and 23Naaq. Specific projects in two general categories are proposed. It will be demonstrated that one can make 1H2O MR images of contrast reagent (CR) distribution volumes directly. This is a very important goal that has not yet been achieved in MRI. It is fundamental, and of utmost significance to more sophisticated applications of CRs. The new technique of combined relaxography and imaging (CRI), recently introduced by this laboratory, is key to the production of distribution volume images. It is explained in this proposal. Studies of cell suspension phantoms, mice, and rats are proposed to demonstrate this approach in vivo. The CRI technique is totally general and applicable to longitudinal, transverse, or rotating-frame NMR relaxation and can be used to study any CR, whether employing the hyperfine or the bulk magnetic susceptibility mechanisms (or both). Longitudinal relaxation and hyperfine CRs are emphasized in this proposal. The yeast cell suspension and rodent studies proposed will also allow the quantitative determination of the extent of compartmental H2O exchange and should permit and production of exchange maps in vivo. The rodent experiments will allow very quantitative measurements of changes in brain CR distribution volumes upon transient disruption of the blood-brain-barrier by non-lethal hyperosmolar intracarotid infusion. Completely analogous 23Na MR studies are proposed. These will employ spectroscopic imaging techniques to make direct distribution volume images of shift reagents (SRs). The main differences expected include the following. Compartmental Na+ exchange is extremely slow and will have no effect on the 23Na spectroscopic images. The electronic charges of the in vivo SR anions are greater than those of the CR anions. Thus, it will be interesting to see if the distribution volumes of the former are at all restricted when compared with those of the latter. This work involves aspects of physics, physical and synthetic chemistry, biophysics, and physiology and has ramifications in the study of a number of pathological conditions including neurological and cardiovascular disorders.